Bergeron Anne, Jorquera Rossana, Tanguay Robert M
Laboratoire de génétique cellulaire et développementale, Département de médecine, pavillon Marchand, Faculté de Médecine, Université Laval, Sainte-Foy, Québec, G1K 7P4 Canada.
Med Sci (Paris). 2003 Oct;19(10):976-80. doi: 10.1051/medsci/20031910976.
Hereditary tyrosinemia type 1 (HT1) is the most severe metabolic disease associated with tyrosine catabolism. An accumulation of toxic metabolites seems responsible for the pathology of HT1. The metabolite fumarylacetoacetate, accumulating due to a deficiency in fumarylacetoacetate hydrolase, displays apoptogenic, mutagenic, aneugenic and mitogenic activities. These effects may underlie the tumorigenic phenomenon observed in HT1. Fumarylacetoacetate in addition to causing disturbances in Ca2+ homeostasis, may induce endoplasmic reticulum stress.
1型遗传性酪氨酸血症（HT1）是与酪氨酸分解代谢相关的最严重的代谢性疾病。有毒代谢产物的积累似乎是HT1发病机制的原因。由于富马酰乙酰乙酸水解酶缺乏而积累的代谢产物富马酰乙酰乙酸具有凋亡、诱变、非整倍体诱导和促有丝分裂活性。这些作用可能是HT1中观察到的致瘤现象的基础。富马酰乙酰乙酸除了会引起钙离子稳态紊乱外，还可能诱导内质网应激。
